Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied a patient with Wilson disease (WD), belonging to a family segregating late-onset, dominant cerebellar ataxia. Analysis of the WD gene showed that the patient is a compound heterozygote, carrying the 14His1069Gln mutation from the father and the 8Gly710Ser mutation from the mother. The 8Gly710Ser is a mutation described previously only in a Swedish patient. Our patient is also homozygous for arylsulfatase A pseudodeficiency. This genetic defect, which has been reported in association with other neuropsychiatric syndromes, has not been described in WD.
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PMID:Detection of a rare Wilson disease mutation associated with arylsulfatase A pseudodeficiency. 1040 72

Metachromatic leukodystrophy (MLD) is a human autosomal recessive lysosomal neurodegenerative disorder that results from the accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA). During adolescence and/or adulthood, there are 2 clinical presentations. It may be that of a degenerative disease of the central nervous system with mainly spastic manifestations or a spino-cerebellar ataxia, or that of a psychosis. As several lines of evidence indicate that the psychotic form of MLD could be a model of psychosis, we decided to do a pluridisciplinary study on 11 psycho-cognitive cases involving mental and psychiatric testing, in comparison with 5 adult motor cases, a biochemical study with enzyme assays and quantitative mass spectrometry of urinary sulfatides, so as to determine whether there were biochemical particularities related to the psychotic forms. For quantitative mass spectrometry (MS), a non physiological sulfatide with C17:0 fatty acid was synthesized. The major sulfatide isoforms were present in the 2 clinical forms with the following fatty acids and sphingoid bases: C22:1/d18:1, and /or C22:0/d18:2 (m/z 862.5), C22:0 (OH)/d18:1 (m/z 878,5), C24:0/d18:1 and / or C24:0/C23:1(OH)/d18:2 (m/z 890,3), C24:0 (OH)/d18:1(m/z 906.5). We had shown previously that there were different ASA mutations in the psychiatric adult form (heterozygous I179S) versus the adult motor form (homozygous P426L). We show here that there were no relations with the level of ASA and with the mass spectrometric study of the sulfatide isoforms which were identical in the 2 clinical forms.
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PMID:Sulfogalactosylceramides in motor and psycho-cognitive adult metachromatic leukodystrophy: relations between clinical, biochemical analysis and molecular aspects. 1798 Jul 9

Spinocerebellar ataxia type15 (SCA15) is a pure ataxia characterized by very slow progression. Only seven families have been identified worldwide, in which partial deletions and a missense mutation of the inositol triphosphate receptor type I gene (ITPR1) have been reported. We examined a four-generation Italian family segregating an autosomal dominant cerebellar ataxia, in which linkage analysis was positive for the SCA15 locus. We performed a genomic real-time polymerase chain reaction to search for ITPR1 gene deletions in this family and in 60 SCA index cases negative for mutations in the SCA1-3, 6-8, 10, 12,and dentatorubral-pallidoluysian atrophy genes. The deleted segments were characterized using a custom array comparative genomic hybridization analysis. We have identified two families with an ITPR1 gene deletion: in one, the deletion involved ITPR1 only, while in the other both sulfatase-modifying factor 1 and ITPR1. Clinical data of ten patients and brain MRI (available for six) showed that the phenotype substantially overlapped known SCA15 cases,but we also noted buccolingual dyskinesias, facial myokymias,and pyramidal signs never reported in SCA15. ITPR1 expression analysis of two deleted cases showed a half dose. Our results further support ITPR1 gene as causative of SCA15. The families reported show that SCA15 is present in Italy and has a greater variability in the age at onset and clinical features than previously reported. We propose that the search for ITPR1 deletions is mandatory in the clinical hypothesis of SCA15 and that ITPR1-reduced expression in blood may be a useful marker to identify SCA15 patients harboring genomic deletions and possibly point mutations causing reduction of mRNA level.
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PMID:Two Italian families with ITPR1 gene deletion presenting a broader phenotype of SCA15. 2008 66

Metachromatic leukodystrophy (MLD) is a rare lysosomal disorder caused by deficient activity of arylsulfatase A or the lack of saposin B, which results in the accumulation of sulfatide in the oligodendrocytes and in the Schwann cells. Three main clinical types of MLD can be distinguished according to the age of onset and the dynamics of clinical outcome: late infantile, juvenile, and adult. We report on a case of late infantile MLD presenting with cerebellar ataxia as the only first clinical sign preceding even changes in white matter visible in MR imaging. The diagnosis was made on the basis of successive MRI, characteristic of demyelination, which developed in the course of the disease, and on the results of the following biochemical and molecular analyses. Very low residual activity of arylsulfatase A was demonstrated in blood leukocytes and the patient was a homozygote for a common mutation c.459+1G>A in the ARSA gene. Since cerebellar ataxia is a relatively common but unspecific neurological symptom in toddlers, it is recommended that MLD be considered as part of the differential diagnosis even if the initial neuroimaging studies are normal and ataxia is the only clinical symptom of the disease.
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PMID:A homozygote for the c.459+1G>A mutation in the ARSA gene presents with cerebellar ataxia as the only first clinical sign of metachromatic leukodystrophy. 2441 7